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      Allogeneic hematopoietic cell transplantation provides effective salvage despite refractory disease or failed prior autologous transplant in angioimmunoblastic T-cell lymphoma: a CIBMTR analysis

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      Journal of Hematology & Oncology
      BioMed Central
      Angioimmunoblastic T-cell lymphoma, Allogeneic transplantation, GVL effects

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          Abstract

          Background

          There is a paucity of data on the role of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with angioimmunoblastic T-cell lymphoma (AITL). Using the CIBMTR registry, we report here the outcomes of AITL patients undergoing an allo-HCT.

          Methods

          We evaluated 249 adult AITL patients who received their first allo-HCT during 2000–2016.

          Results

          The median patient age was 56 years (range = 21–77). Majority of the patients were Caucasians (86%), with a male predominance (60%). Graft-versus-host disease (GVHD) prophylaxis was predominantly calcineurin inhibitor-based approaches while the most common graft source was peripheral blood (97%). Median follow-up of survivors was 49 months (range = 4–170 months). The cumulative incidence of grade 2–4 and grade 3–4 acute GVHD at day 180 were 36% (95% CI = 30–42) and 12 (95% CI = 8–17), respectively. The cumulative incidence of chronic GVHD at 1 year was 49% (95%CI 43–56). The 1-year non-relapse mortality (NRM) was 19% (95% CI = 14–24), while the 4-year relapse/progression, progression-free survival (PFS), and overall survival (OS) were 21% (95% CI = 16–27), 49% (95% CI = 42–56), and 56% (95% CI = 49–63), respectively. On multivariate analysis, chemoresistant status at the time of allo-HCT was associated with a significantly higher risk for therapy failure (inverse of PFS) (RR = 1.73 95% CI = 1.08–2.77), while KPS < 90% was associated with a significantly higher risk of mortality (inverse of OS) (RR = 3.46 95% CI = 1.75–6.87).

          Conclusion

          Our analysis shows that allo-HCT provides durable disease control even in AITL patients who failed a prior auto-HCT and in those subjects with refractory disease at the time of allografting.

          Electronic supplementary material

          The online version of this article (10.1186/s13045-018-0696-z) contains supplementary material, which is available to authorized users.

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          Most cited references16

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          Chronic graft-versus-host syndrome in man

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            Hematopoietic cell transplantation for systemic mature T-cell non-Hodgkin lymphoma.

            To analyze outcomes of hematopoietic cell transplantation (HCT) in T-cell non-Hodgkin lymphoma.
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              Graft-versus-lymphoma effect for aggressive T-cell lymphomas in adults: a study by the Société Francaise de Greffe de Moëlle et de Thérapie Cellulaire.

              Aggressive T-cell lymphomas (ATCLs) represent 10% to 15% of non-Hodgkin's lymphomas (NHLs) in adults. ATCLs show a worse prognosis than B-cell lymphomas. On behalf of the Société Française de Greffe de Moëlle et de Thérapie Cellulaire, we conducted a retrospective analysis including 77 ATCL patients who underwent allogeneic stem-cell transplantation (alloSCT). The different diagnosis included anaplastic large-cell lymphoma (ALCL; n = 27), peripheral T-cell lymphoma not otherwise specified (PTCL-NOS; n = 27), angioimmunoblastic T-cell lymphoma (AITL; n = 11), hepatosplenic gamma/delta lymphoma (HSL; n = 3), T-cell granular lymphocytic leukemia (T-GLL; n = 1), nasal natural killer (NK)/T-cell lymphoma (nasal-NK/L; n = 3) or non-nasal NK/T-cell lymphoma (non-nasal-NK/L; n = 2), enteropathy-type T-cell (n = 1), and human T-lymphotropic virus (HTLV)-1 lymphoma (n = 2). Fifty-seven patients received a myeloablative conditioning regimen. Donors were human leukocyte antigen (HLA)-matched in 70 cases and related in 60 cases. Thirty-one patients were in complete remission (CR) at the time of alloSCT, whereas 26 were in partial response (PR). Five-year toxicity-related mortality (TRM) incidence was 33% (95% CI, 24% to 46%). The 5-year overall survival (OS) and event-free survival (EFS) rates were 57% (95% CI, 45% to 68%) and 53% (95% CI, 41% to 64%), respectively. In multivariate analysis, chemoresistant disease (stable, refractory, or progressing disease) at the time of alloSCT and the occurrence of severe grade 3 to 4 acute graft-versus-host disease (aGVHD) were the strongest adverse prognostic factors for OS (P = .03 and .03, respectively). Disease status at transplantation significantly influenced the 5-year EFS (P = .003), and an HLA-mismatched donor increased TRM (P = .04). We conclude that alloSCT is a potentially efficient therapy for NK/T lymphomas and is worth further investigation through prospective clinical trials.
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                Author and article information

                Contributors
                Narendranath.Epperla@osumc.edu
                kwooahn@mcw.edu
                clitovich@mcw.edu
                sahmed3@mdanderson.org
                minoo.battiwalla@hcahealthcare.com
                jonathon.cohen@emory.edu
                dahip@mskcc.org
                nosha.farhadfar@medicine.ufl.edu
                umar-farooq@uiowa.edu
                cesar.freytes@hcahealthcare.com
                nilanjan.ghosh@carolinashealthcare.org
                Bradley.haverkos@ucdenver.edu
                aherrera@coh.org
                mhertzberg10@gmail.com
                gerhard.hildebrandt@uky.edu
                inwards.david@mayo.edu
                kharfandabaja.mohamed@mayo.edu
                farhad.khimani@moffitt.org
                hml@case.edu
                aleksandr.lazaryan@moffitt.org
                llekakis@med.miami.edu
                hemant.murthy@medicine.ufl.edu
                sunita_nathan@rush.edu
                taiga.nishihori@moffitt.org
                pawarode@med.umich.edu
                timp@adhb.govt.nz
                praveen.ramakrishnan@utsouthwestern.edu
                arezvani@stanford.edu
                rizwan_romee@dfci.harvard.edu
                nishah@mcw.edu
                asureda@iconcologia.net
                tfenske@mcw.edu
                414-805-0643 , mhamadani@mcw.edu
                Journal
                J Hematol Oncol
                J Hematol Oncol
                Journal of Hematology & Oncology
                BioMed Central (London )
                1756-8722
                10 January 2019
                10 January 2019
                2019
                : 12
                : 6
                Affiliations
                [1 ]ISNI 0000 0001 2285 7943, GRID grid.261331.4, Division of Hematology, Department of Medicine, , The James Cancer Hospital and Solove Research Institute, The Ohio State University, ; 460 W 10th Ave, Columbus, OH 43210 USA
                [2 ]ISNI 0000 0001 2111 8460, GRID grid.30760.32, Center for International Blood and Marrow Transplant Research, Department of Medicine, , Medical College of Wisconsin, ; 9200 W. Wisconsin Avenue, Suite C5500, 8701 W. Watertown Plank Rd, Milwaukee, WI 53226 USA
                [3 ]ISNI 0000 0001 2291 4776, GRID grid.240145.6, M.D. Anderson Cancer Center, ; 1515 Holcombe Boulevard, Houston, TX 77030 USA
                [4 ]ISNI 0000 0004 0459 5478, GRID grid.419513.b, Sarah Cannon BMT Program, ; 2400 Patterson St. Suite 215, Nashville, TN 37206 USA
                [5 ]ISNI 0000 0001 0941 6502, GRID grid.189967.8, Winship Cancer Institute, Emory University School of Medicine, ; 1365-C Clifton Road NE, Atlanta, GA 30322 USA
                [6 ]ISNI 0000 0001 2171 9952, GRID grid.51462.34, Memorial Sloan Kettering Cancer Center, ; 1275 York Ave., New York, NY 10065 USA
                [7 ]ISNI 0000 0004 1936 8091, GRID grid.15276.37, Shands Healthcare and University of Florida, ; PO Box 100278, Gainesville, FL 32610 USA
                [8 ]ISNI 0000 0004 0434 9816, GRID grid.412584.e, University of Iowa Hospitals and Clinics, ; 200 Hawkins Drive C332 GH, Iowa City, IA 52242 USA
                [9 ]GRID grid.419930.6, Texas Transplant Institute, ; 4410 Medical Drive Suite 410, San Antonio, TX 78229 USA
                [10 ]GRID grid.468189.a, Levine Cancer Institute, ; 1021 Morehead Medical Drive Suite 5300, Charlotte, NC 28204 USA
                [11 ]ISNI 0000 0000 9908 7089, GRID grid.413085.b, University of Colorado Hospital, ; 1665 Aurora Court F-754, Aurora, CO 80045 USA
                [12 ]ISNI 0000 0004 0421 8357, GRID grid.410425.6, City of Hope National Medical Center, ; 1500 E Duarte Rd, Duarte, CA 91010 USA
                [13 ]GRID grid.415193.b, Prince of Wales Hospital, ; SEALS Level 4 Campus Building, Barker Street, Randwick, NSW 2031 Australia
                [14 ]ISNI 0000 0004 0402 4392, GRID grid.461341.5, University of Kentucky Chandler Medical Center, ; 800 Rose Street CC 301, Lexington, KY 40536 USA
                [15 ]ISNI 0000 0004 0459 167X, GRID grid.66875.3a, Mayo Clinic Rochester, ; 200 First Street SW, Rochester, MN 55902 USA
                [16 ]ISNI 0000 0004 0443 9942, GRID grid.417467.7, Mayo Clinic, ; 4500 San Pablo Rd, Jacksonville, FL 32224 USA
                [17 ]ISNI 0000 0000 9891 5233, GRID grid.468198.a, H. Lee Moffitt Cancer Center and Research Institute, ; 12902 Magnolia Drive, Tampa, FL 33612 USA
                [18 ]ISNI 0000 0001 2164 3847, GRID grid.67105.35, Case Western Reserve University, ; 11100 Euclid Ave, Cleveland, OH 44106 USA
                [19 ]ISNI 0000 0004 1936 8606, GRID grid.26790.3a, Univeristy of Miami, ; 1475 NW 12th Ave, Miami, FL 33136 USA
                [20 ]ISNI 0000 0001 2353 285X, GRID grid.170693.a, Division of Hematology/Oncology, , University Florida College of Medicine, ; 12902 Magnolia Drive, Tampa, FL 33612 USA
                [21 ]ISNI 0000 0001 0705 3621, GRID grid.240684.c, Rush University Medical Center, ; 849 North Franklin Street Unit 1503, Chicago, IL 60610 USA
                [22 ]ISNI 0000000086837370, GRID grid.214458.e, The University of Michigan, ; 322 E Liberty St. Unit 4, Ann Arbor, MI 48104 USA
                [23 ]ISNI 0000 0000 9567 6206, GRID grid.414054.0, Starship Children’s Health, Level 7 Blood and Cancer Center Park Road, ; Grafton, Auckland, 1142 New Zealand
                [24 ]UT Southwestern Medical Center – BMT Program, 7800C Stenton Ave. Apt. 210, Philadelphia, PA 19118 USA
                [25 ]ISNI 0000 0004 5997 482X, GRID grid.490568.6, Stanford Health Care, ; 300 Pasteur Drive, Room H0101 MC 5623, Stanford, CA 94305 USA
                [26 ]ISNI 0000 0001 2106 9910, GRID grid.65499.37, Dana Farber Cancer Institute - Adults, ; 450 Brookline Avenue, Boston, MA 02215 USA
                [27 ]ISNI 0000 0001 2111 8460, GRID grid.30760.32, Division of Hematology and Oncology, Department of Medicine, , Medical College of Wisconsin, ; 8701 Watertown Plank Rd. PO Box 26509, Milwaukee, WI 53226 USA
                [28 ]Institut Català d’Oncologia - Hospital Duran I Reynals, Avda. Granvfa 199-203, 08908 Barcelona, Spain
                Article
                696
                10.1186/s13045-018-0696-z
                6329157
                30630534
                151dddb1-dcd0-4abd-8bec-a890ad4402e4
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 2 November 2018
                : 27 December 2018
                Categories
                Research
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                © The Author(s) 2019

                Oncology & Radiotherapy
                angioimmunoblastic t-cell lymphoma,allogeneic transplantation,gvl effects

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